P718: ASCIMINIB MANAGED-ACCESS PROGRAM (MAP) IN RUSSIA
Authors: O. Shukhov, A. Turkina, E. Lomaia, E. Morozova, A. Petrova, T. Chitanava, Y. Vlasova, E. Chelysheva, E. Kuzmina, I. Nemchenko, A. Bykova, M. Gurianova, A. Kohno, E. Parovichnikova
Journal: HemaSphere (2022)

Background: Asciminib is aa ABL kinase inhibitor that works by Specifically Targeting the ABL Myristoyl Pocket (STAMP) that has shown efficacy and a good safety profile in phase I and III studies in patients with Ph-positive leukemia failing prior TKIs. In Russia, asciminib is available under the Novartis approved Managed Access Program (MAP). Aims: to present interim results of the use of aciminib in clinical practice under the MAP program in Russia. Methods: From September 2019 to January 2022, 68 patients (pts) with CML were enrolled in the MAP program from three Russian clinics. We analyzed therapy results from 50 pts. Eleven pts who received asciminib for less than 3 months and 7 pts who underwent bone marrow transplantation were excluded from the analysis. Pts recruitment, dosing regimen, response monitoring, and toxicity control were performed according to the MAP treatment plan. Complete cytogenetic response (CCyR), major molecular response (MMR) and deep molecular response (MR4) were assessed by cumulative incident function (CIF) with Gray’s test for comparison responses in subgroups. Multivariate analysis was performed to find independent factors for MMR. Differences were considered significant if the p ≤ 0.05 Results: Baseline characteristics: female 66%; Ме age 53 years (range 26-81); median duration of CML before asciminib 8 years (range 1-24); 42 pts were in chronic phase (CP) CML, 7 and 1 pts had a history of accelerated phase (AP) and myeloid blast crisis (MBC), respectively. Twenty nine (58%) pts had BCR::ABL1 mutations, 20 pts (40%) had BCR::ABL1T315I, 8 (16%) pts had at least two mutations. Eight (16%) pts had additional chromosomal abnormalities (ACAs). Among the thirty three (66%) pts who received ≥4 TKIs, 20 (40%) had a history of ponatinib treatment. Me follow-up period was 11 months (range 4-30), 7(14%) pts discontinued asciminib (5 due to resistance, 2 due to progression). One-year survival rate without treatment discontinuation was 92%. In 30 (60%) pts, The initial dose was 40 BID in 30 (60%) pts and 200 mg BID in 20 (40%) pts The 2-year overall survival was 96%, two (4%) pts progressed to advanced phase and died. CIF of CCyR, MMR and MR4 at 12 month was 37.5% (CI:24-58), 32% (CI:20-52) and 14% (CI:7-31), respectively. Univariate analysis was performed for the following factors: history of advanced phases, initial dose of asciminib, presence of BCR::ABL1 mutations and ACAs, best molecular response on previous TKIs, molecular response at the time of asciminib starting, history of ponatinib treatment, number of prior TKIs and duration of TKI therapy before asciminib. Best molecular response to previous TKIs, molecular response at the time of asciminib starting, number of TKIs prior to asciminib, and history of previous ponatinib treatment were identified as predictors of MMR at 12 months (Table 1). Best molecular response on previous TKIs (≤1% vs 1-10% vs ≥10%) was found to be independently significant factor due to multivariate analysis (p=0,0072, hazard ratio 7,6 (1,7-33)) Twenty two (44%) patients experienced adverse events (AEs) of any grade and 8 (16%) had AEs of grade 3-4 (Table 2), reported during treatment, regardless of the connection with the drug. No one stopped treatment because of toxicity. No differences in toxicity were found between doses of 80 and 400 mg/day. Image:Summary/Conclusion: Asciminib shows promising results for the treatment of highly pre-treated CML patients and should be considered as an therapeutic options for pts with failure to previous TKIs